A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial.

BACKGROUND: Nasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia. METHODS: In the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured. RESULTS: The primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 - -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 - 1.13, p = 0.066). In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 - 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 - 99); median (range) in the LFO group: 14.5 (0 - 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674). CONCLUSIONS: Respiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF. TRIAL REGISTRATION: jRCTs072190021 . The full date of first registration on jRCT: August 26, 2019.

Influence of N95 Mask-related Hypoxemia on Headache, Stress, Anxiety, and Quality of Sleep during COVID-19 Patient Care among Frontline Health Care Professionals.

BACKGROUND: Prolonged use of N95 masks by healthcare workers might affect physical health due to mask-related hypoxia in addition to the psychological effects of N95 masks. We tried to explore the association of N95 mask-related hypoxia and headache with stress, quality of sleep, and anxiety in the current study. MATERIALS AND METHODS: The sample (N = 78) consisted of 41 doctors and 37 nurses involved in COVID-19 patient care and using N95 masks with or without PPE for at least 4 hours. Perceived stress scale (PSS), Coronavirus anxiety scale (CAS), and Pittsburgh sleep quality index (PSQI) were administered, and physical parameters like heart rate and oxygen saturation (SpO2) were measured. RESULTS: Around 42% of the study participants experienced headaches after wearing an N95 mask and had a higher increase in heart rate (mean percent:10.5% vs 6.3%) and decline in SpO2 (mean percent: 2.6% vs 1.5%) compared to those who didn't develop a headache after N95 mask use. Independent samples t-test showed a mean difference for PSS and CAS between those who experienced headaches and those who didn't. The mean PSQI scores among the study participants were 8.91 ± 5.78; the score among those participants with and without headache was 10.57 ± 3.11 and 7.68 ± 2.53, respectively. CONCLUSION: Perceived corona anxiety, poor sleep quality, and corona anxiety are associated with N95-related headaches and SpO2 drop among health professionals who wear N95 masks for at least 4 hours.

[Follow-up of patients after COVID-19 pneumonia. Pulmonary sequelae]. / Seguimiento de los pacientes después de neumonía por COVID-19. Secuelas pulmonares.

Coronavirus disease 2019 (COVID-19) is an infection caused by SARS-CoV-2 that has caused an unprecedented pandemic with a high rate of morbidity and mortality worldwide. Although most cases are mild, there are a considerable number of patients who develop pneumonia or even acute respiratory distress syndrome (ARDS). After having recovered from the initial disease, many patients continue with various symptoms (fatigue, dry cough, fever, dyspnea, anosmia, and chest pain, among others.), which has led to consider the possible existence of "post-COVID-19 syndrome". Although the definition and validity of this syndrome are not clear yet, several studies report that individuals who have recovered from COVID-19 may have persistent symptoms, radiological abnormalities, and compromised respiratory function. Current evidence suggests that there is a large number of pulmonary sequelae after COVID-19 pneumonia (interstitial thickening, ground glass opacities, crazy paving pattern, and bronchiectasis, among others.). Likewise, it seems that pulmonary function tests (spirometry, DLCO, 6MWT, and measurement of maximum respiratory pressures), in addition to high-resolution computed axial tomographies (CAT scan), are useful for the assessment of these post-COVID-19 pulmonary sequelae. This review aims to describe the possible pulmonary sequelae after COVID-19 pneumonia, as well as to suggest diagnostic procedures for their correct assessment and follow-up; thus, allowing proper management by a multidisciplinary medical team.

COVID-19 es la enfermedad causada por el virus SARS-CoV-2, la cual ha ocasionado una pandemia sin precedentes, con gran cantidad de infectados y muertos en el mundo. Aunque la mayoría de los casos son leves, existe una cantidad considerable de pacientes que desarrollan neumonía o, incluso, síndrome de distrés respiratorio agudo (SDRA). Luego de recuperarse del cuadro inicial, muchos pacientes continúan con diversos síntomas (fatiga, tos seca, fiebre, disnea, anosmia, dolor torácico, entre otras), lo que ha llevado a considerar la posible existencia del "síndrome pos-COVID-19". Aunque la definición y validez de este síndrome aún no son claras, varios estudios reportan que los individuos recuperados de la COVID-19 pueden tener persistencia de síntomas, anormalidades radiológicas y compromiso en la función respiratoria. La evidencia actual sugiere que existe gran cantidad de secuelas pulmonares despues de una neumonía por COVID-19 (engrosamiento intersticial, infiltrado en vidrio esmerilado, patrón en empedrado, bronquiectasias, entre otras.). De igual forma, parece ser que las pruebas de función pulmonar (espirometría, prueba de difusión pulmonar de monóxido de carbono, prueba de caminata de seis minutos y la medición de las presiones respiratorias máximas), además de la tomografía axial computarizada de alta resolución, son útiles para evaluar las secuelas pulmonares pos-COVID-19. En esta revisión se pretende describir las posibles secuelas a nivel pulmonar posteriores a neumonía por COVID-19, así como sugerir procedimientos diagnósticos para su correcta evaluación y seguimiento, que permitan el manejo adecuado por parte de un equipo médico multidisciplinario.

The Clinical Utility of Relative Bradycardia for Identifying Cases of Coronavirus Disease 2019 Pneumonia: A Retrospective Pneumonia Cohort Study.

Objective Both coronavirus disease 2019 (COVID-19) pneumonia and relative bradycardia are common conditions among clinicians; however, the association between these has not been well studied. The present study assessed whether or not relative bradycardia on admission was more predominant in patients with COVID-19 pneumonia than in those with other infectious pneumonia. Methods For this single-center, retrospective cohort study, we collected data through electronic medical records and examined the occurrence of relative bradycardia on admission. We used logistic regression analyses to compare outcomes with and without relative bradycardia on admission. The primary outcome was COVID-19 pneumonia. The secondary outcome was hypoxemia during the hospital stay. We performed multivariable regression with adjusting for the effects of age, sex, healthcare-associated pneumonia, body mass index, Charlson comorbidity index, and bilateral infiltration on computed tomography (CT) as confounding factors. Patients Adult patients with new-onset hospitalized infectious pneumonia confirmed by CT between January 1, 2020, and July 31, 2021. Results This study included 395 participants. On admission, 87 (22.0%) participants exhibited relative bradycardia, and 302 (76.5%) participants had COVID-19. Relative bradycardia on admission was not significantly associated with COVID-19 pneumonia [adjusted odds ratio (OR) 1.32; 95% confidence interval (CI) 0.49-3.54, p=0.588] but was associated with hypoxemia (adjusted OR 4.74; 95%CI 2.64-8.52, p<0.001). Conclusion The study results showed that relative bradycardia on admission was not associated with COVID-19 in cases of infectious pneumonia. However, relative bradycardia may be associated with the incidence of hypoxemia in pneumonia.

Oxygenated right ventricular assist device as part of veno-venopulmonary extracorporeal membrane oxygenation to support the right ventricle and pulmonary vasculature.

COVID-19 infection can lead to severe acute respiratory distress syndrome (ARDS), right ventricular (RV) failure and pulmonary hypertension. Venovenous extracorporeal membrane oxygenation (V-V ECMO) has been used for patients with refractory hypoxemia. More recently dual-lumen right atrium to pulmonary artery oxygenated right ventricular assist devices (Oxy-RVAD) have been utilized in the severe medical refractory COVID ARDS setting. Historically, animal data has demonstrated that high continuous non-pulsatile RVAD flows, leading to unregulated and unprotected circulation through the pulmonary vessels is associated with an increased risk of pulmonary hemorrhage and increased amount of extravascular lung water. These risks are heightened in the setting of ARDS with fragile capillaries, left ventricular (LV) diastolic failure, COVID cardiomyopathy, and anticoagulation. Concurrently, due to infection, tachycardia, and refractory hypoxemia, high V-V ECMO flows to match high cardiac output are often necessary to maintain systemic oxygenation. Increase in cardiac output without a concurrent increase in VV ECMO flow will result in a higher fraction of deoxygenated blood returning to the right heart and therefore resulting in hypoxemia. Several groups have suggested using a RVAD only strategy in COVID ARDS; however, this exposes the patients to the risk of pulmonary hemorrhage. We present one of the first known cases using an RV mechanical support, partial flow pulmonary circulation, oxygenated Veno-venopulmonary (V-VP) strategy resulting in RV recovery, total renal recovery, awake rehabilitation, and recovery.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]). INTERPRETATION: In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

Hypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin? / Hypoxische, anämische und kardial bedingte Hypoxämie: Wann beginnt die Hypoxie im Gewebe?

In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. While restrictive and generally accepted rules are specified in the transfusion guidelines for anemic hypoxemia, in the case of hypoxic hypoxia, the indication for invasive ventilation is made very early. The clinical assessment and indication are limited to the parameters oxygen saturation, oxygen partial pressure and oxygenation index. During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.

Pathophysiology of Hypoxemia in COVID-19 Lung Disease.

As the pandemic has progressed, our understanding of hypoxemia in coronavirus disease 2019 (COVID-19) lung disease has become more nuanced, although much remains to be understood. In this article, we review ventilation-perfusion mismatching in COVID-19 and the evidence to support various biologic theories offered in explanation. In addition, the relationship between hypoxemia and other features of severe COVID-19 lung disease such as respiratory symptoms, radiographic abnormalities, and pulmonary mechanics is explored. Recognizing and understanding hypoxemia in COVID-19 lung disease remains essential for risk stratification, prognostication, and choice of appropriate treatments in severe COVID-19.

Non-invasive support for the hypoxaemic patient.

Optimisation of oxygenation strategies in patients with hypoxaemic respiratory failure is a top priority for acute care physicians, as hypoxaemic respiratory failure is one of the leading causes of admission. Various oxygenation methods range from non-invasive face masks to high flow nasal cannulae, which have advantages and disadvantages for this heterogeneous patient group. Focus has turned toward examining the benefits of non-invasive ventilation, as this was heavily researched in resource-limited settings during the COVID-19 pandemic. The oxygenation strategy should be determined on an individualised basis for patients, and with new evidence from the COVID-19 pandemic, providers may now consider placing further emphasis on non-invasive approaches. As non-invasive ventilation continues to be used in increasing frequency, new methods of monitoring patient response, including when to escalate ventilation strategy, will need to be validated.

COVID-19 in patients with myasthenia gravis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG). METHODS: We studied the clinical course of COVID-19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle-specific tyrosine kinase antibodies) between April 1, 2020-April 30-2020. RESULTS: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID-19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications. DISCUSSION: Our findings suggest that the clinical course and outcomes in patients with MG and COVID-19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.

Hospitalised COVID-19 outcomes are predicted by hypoxaemia and pneumonia phenotype irrespective of the timing of their emergence.

Despite the known clinical importance of hypoxemia and pneumonia, there is a paucity of evidence for these variables with respect to risk of mortality and short-term outcomes among those hospitalised with COVID-19. OBJECTIVE: Describe the prevalence and clinical course of patients hospitalised with COVID-19 based on oxygenation and pneumonia status at presentation and determine the incidence of emergent hypoxaemia or radiographic pneumonia during admission. METHODS: A retrospective study was conducted using a Canadian regional registry. Patients were stratified according to hypoxaemia/pneumonia phenotype and prevalence. Clinical parameters were compared between phenotypes using χ2 and one-way Analysis of variance (ANOVA). Cox analysis estimated adjusted Hazard Ratios (HR) for associations between disease outcomes and phenotypes. RESULTS: At emergency department (ED) admission, the prevalence of pneumonia and hypoxaemia was 43% and 50%, respectively, and when stratified to phenotypes: 28.2% hypoxaemia+/pneumonia+, 22.2% hypoxaemia+/pneumonia-, 14.5% hypoxaemia-/pneumonia+ and 35.1% hypoxaemia-/pneumonia-. Mortality was 31.1% in the hypoxaemia+/pneumonia- group and 26.3% in the hypoxaemia+/pneumonia+ group. Hypoxaemia with pneumonia and without pneumonia predicted higher probability of death. Hypoxaemia either <24 hours or ≥24 hours after hospitalisation predicted higher mortality and need for home oxygen compared with those without hypoxaemia. Patients with early hypoxaemia had higher probability of Intensive care unit (ICU) admission compared with those with late hypoxaemia. CONCLUSION: Mortality in COVID-19 infection is predicted by hypoxaemia with or without pneumonia and was greatest in patients who initially presented with hypoxaemia. The emergence of hypoxaemia was predicted by radiographic pneumonia. Patients with early and emergent hypoxaemia had similar mortality but were less likely to be admitted to ICU. There may be delayed identification of hypoxaemia, which prevents timely escalation of care.

Ventilatory Failure And Pulmonary Embolism In Covid-19 Requiring Enhanced Venous Drainage For Extracorporeal Membrane Oxygenation.

COVID-19 infection manifests as a spectrum of respiratory and vascular complications, including acute respiratory distress syndrome (ARDS) and pulmonary embolism. Herein, we describe a case of a healthy young male who presented with ARDS refractory to mechanical ventilation and concomitant bilateral pulmonary emboli managed with extracorporeal membrane oxygenation (ECMO) and embolectomy. The embolectomy and initial veno-venous ECMO configuration failed to correct the patient's hypoxemia despite maximal flows. This was thought to be due to a high-output state secondary to vasodilatory shock preventing adequate drainage from the existing single drainage ECMO cannulation, following which a second venous cannula was placed to form a unique veno-veno-venous ECMO circuit that resolved the persistent hypoxemia. The case underscores the importance of identifying embolic events and vasodilatory shock in COVID-19 patients, both of which need to be addressed simultaneously to avoid worsening right ventricular failure (via both mechanical and hypoxia-driven pathways) and the resulting veno-arterial ECMO along with its associated complications.